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The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice
(2018)
The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.
The search for life on Mars and in the Solar System - strategies, logistics and infrastructures
(2018)
The question "Are we alone in the Universe?" is perhaps the most fundamental one that affects mankind. How can we address the search for life in our Solar System? Mars, Enceladus and Europa are the focus of the search for life outside the terrestrial biosphere. While it is more likely to find remnants of life (fossils of extinct life) on Mars because of its past short time window of the surface habitability, it is probably more likely to find traces of extant life on the icy moons and ocean worlds of Jupiter and Saturn. Nevertheless, even on Mars there could still be a chance to find extant life in niches near to the surface or in just discovered subglacial lakes beneath the South Pole ice cap. Here, the different approaches for the detection of traces of life in the form of biosignatures including pre-biotic molecules will be presented. We will outline the required infrastructure for this enterprise and give examples of future mission concepts to investigate the presence of life on other planets and moons. Finally, we will provide suggestions on methods, techniques, operations and strategies for preparation and realization of future life detection missions.
During the development of a Competence Developing Game’s (CDG) story it is indispensable to understand the target audience. Thereby, CDGs stories represent more than just the plot. The Story is about the
Setting, the Characters and the Plot. As a toolkit to support the
development of such a story, this paper introduces the UserFocused Storybuilding (short UFoS) Framework for CDGs. The Framework and its utilization will be explained, followed by a description of its development and derivation, including an empirical study. In addition, to simplify the Framework use regarding the CDG’s target audience, a new concept of Nine Psychographic Player Types will be explained. This concept of Player Types provides an approach to handle the differences in between players during the UFoS Framework use. Thereby,
this article presents a unique approach to the development of
target group-differentiated CDGs stories.
In this article, we present an overview on the thermocatalytic reaction of hydrogen peroxide (H₂O₂) gas on a manganese (IV) oxide (MnO₂) catalytic structure. The principle of operation and manufacturing techniques are introduced for a calorimetric H₂O₂ gas sensor based on porous MnO₂. Results from surface analyses by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) of the catalytic material provide indication of the H₂O₂ dissociation reaction schemes. The correlation between theory and the experiments is documented in numerical models of the catalytic reaction. The aim of the numerical models is to provide further information on the reaction kinetics and performance enhancement of the porous MnO₂ catalyst.
In energy economy forecasts of different time series are rudimentary. In this study, a prediction for the German day-ahead spot market is created with Apache Spark and R. It is just an example for many different applications in virtual power plant environments. Other examples of use as intraday price processes, load processes of machines or electric vehicles, real time energy loads of photovoltaic systems and many more time series need to be analysed and predicted.
This work gives a short introduction into the project where this study is settled. It describes the time series methods that are used in energy industry for forecasts shortly. As programming technique Apache Spark, which is a strong cluster computing technology, is utilised. Today, single time series can be predicted. The focus of this work is on developing a method to parallel forecasting, to process multiple time series simultaneously with R and Apache Spark.
Nanotubular tobacco mosaic virus (TMV) particles and RNA-free lower-order coat protein (CP) aggregates have been employed as enzyme carriers in different diagnostic layouts and compared for their influence on biosensor performance. In the following, we describe a label-free electrochemical biosensor for improved glucose detection by use of TMV adapters and the enzyme glucose oxidase (GOD). A specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CP aggregates was achieved via bioaffinity binding. Glucose sensors with adsorptively immobilized [SA]-GOD, and with [SA]-GOD cross-linked with glutardialdehyde, respectively, were tested in parallel on the same sensor chip. Comparison of these sensors revealed that TMV adapters enhanced the amperometric glucose detection remarkably, conveying highest sensitivity, an extended linear detection range and fastest response times. These results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for applications in biosensorics and biochips. Here, we describe the fabrication and use of amperometric sensor chips combining an array of circular Pt electrodes, their loading with GOD-modified TMV nanotubes (and other GOD immobilization methods), and the subsequent investigations of the sensor performance.
Monitoring of organic acids (OA) and volatile fatty acids (VFA) is crucial for the control of anaerobic digestion. In case of unstable process conditions, an accumulation of these intermediates occurs. In the present work, two different enzyme-based biosensor arrays are combined and presented for facile electrochemical determination of several process-relevant analytes. Each biosensor utilizes a platinum sensor chip (14 × 14 mm²) with five individual working electrodes. The OA biosensor enables simultaneous measurement of ethanol, formate, d- and l-lactate, based on a bi-enzymatic detection principle. The second VFA biosensor provides an amperometric platform for quantification of acetate and propionate, mediated by oxidation of hydrogen peroxide. The cross-sensitivity of both biosensors toward potential interferents, typically present in fermentation samples, was investigated. The potential for practical application in complex media was successfully demonstrated in spiked sludge samples collected from three different biogas plants. Thereby, the results obtained by both of the biosensors were in good agreement to the applied reference measurements by photometry and gas chromatography, respectively. The proposed hybrid biosensor system was also used for long-term monitoring of a lab-scale biogas reactor (0.01 m³) for a period of 2 months. In combination with typically monitored parameters, such as gas quality, pH and FOS/TAC (volatile organic acids/total anorganic carbonate), the amperometric measurements of OA and VFA concentration could enhance the understanding of ongoing fermentation processes.
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) today are widely used for the investigation of normal electromechanical cardiac function, of cardiac medication and of mutations. Computational models are thus established that simulate the behavior of this kind of cells. This section first motivates the modeling of hiPS-CM and then presents and discusses several modeling approaches of microscopic and macroscopic constituents of human-induced pluripotent stem cell-derived and mature human cardiac tissue. The focus is led on the mapping of the computational results one can achieve with these models onto mature human cardiomyocyte models, the latter being the real matter of interest. Model adaptivity is the key feature that is discussed because it opens the way for modeling various biological effects like biological variability, medication, mutation and phenotypical expression. We compare the computational with experimental results with respect to normal cardiac function and with respect to inotropic and chronotropic drug effects. The section closes with a discussion on the status quo of the specificity of computational models and on what challenges have to be solved to reach patient-specificity.
The continuing growth of scientific publications raises the question how research processes can be digitalized and thus realized more productively. Especially in information technology fields, research practice is characterized by a rapidly growing volume of publications. For the search process various information systems exist. However, the analysis of the published content is still a highly manual task. Therefore, we propose a text analytics system that allows a fully digitalized analysis of literature sources. We have realized a prototype by using EBSCO Discovery Service in combination with IBM Watson Explorer and demonstrated the results in real-life research projects. Potential addressees are research institutions, consulting firms, and decision-makers in politics and business practice.
Nach einem intensiven politischen Diskurs wurde im vergangenen Jahr die Datenschutz-Grundverordnung (DSGVO) verabschiedet. Die DSGVO ersetzt zum 25.5.2018 die bislang geltende, aus dem Jahre 1995 stammende Datenschutz-Richtlinie 95/46/EG. Die Novellierung des Datenschutzrechts bringt zahlreiche neue Anforderungen mit sich. Unternehmen sind daher gezwungen, sich auf die Änderungen einzustellen, ihre datenschutzrelevanten Prozesse im Hinblick auf die neuen Anforderungen zu überprüfen und bis zum Mai 2018 an der DSGVO auszurichten. Der Beitrag gibt einen kurzen Überblick über die zentralen Aspekte der Datenschutzreform und die damit einhergehenden Herausforderungen für Unternehmen.
Angesichts des anhaltenden Wachstums wissenschaftlicher Veröffentlichungen werden Instrumente benötigt, um Literaturanalysen durch Digitalisierung produktiver zu gestalten. Dieser Beitrag stellt einen Ansatz vor, der bibliographische Daten aus der Literaturdatenbank EBSCO Discovery Service mithilfe von Text-Analytics-Methoden erschließt. Die Lösung basiert auf dem Textanalysesystem IBM Watson Explorer und eignet sich für explorative Literaturanalysen, um beispielsweise den Status quo emergierender Technologiefelder in der Literatur zu reflektieren. Die generierten Ergebnisse sind in den Kontext der zunehmenden Werkzeugunterstützung des Literaturrechercheprozesses einzuordnen und können für intra- sowie interinstitutionelle Wissenstransferprozesse in Forschungs- und Beratungskontexten genutzt werden.
Zusammenfassung: In der Orthopädie zählt der therapeutische Ultraschall als Mittel zur Prävention und Therapiebegleitung. Er hat mechanische, thermische und physiko-chemische Auswirkungen auf den menschlichen Körper. Um mehr Erkenntnisse über die thermischen Auswirkungen zu erlangen, wurden Versuche an einem Hydrogel-Phantom und an Probanden durchgeführt. Dabei entstand eine signifikante Erwärmung des Gewebes, welche beim Probandenversuch an der Oberfläche und beim Hydrogelversuch in der Tiefe gemessen wurde.
Summary: In orthopaedics, therapeutic ultrasound is a tool of prevention and therapy support. It has mechanical, thermal and physico-chemical effects on the human body. Tests with a hydrogel phantom and with human probands have been performed in order to obtain more knowledge about their thermal effects. Both tests measured temperature increases in cell tissue, on the surface with the human proband test and in depth with the hydrogel phantom test.